Histo: Renal Disease Pt.2

Question 1

How does acute tubular injury lead to reduced GFR?

Answer 1

• Blockage of tubules by casts
• Leakage from tubules into interstitial space
• Secondary haemodynamic changes

Question 2

Describe the histological appearance of ATN

Answer 2

Necrosis of short segments of tubules

Question 3

What is acute tubulo-interstitial nephritis?

Answer 3

Inflammation of the renal interstitium, typically due to immune-mediated hypersensitivity reaction

Can be caused by infection and drugs (NSAIDs, antibiotics, diuretics, allopurinol, PPIs)

Question 4

Describe the histological appearance of acute tubulo-interstital nephritis.

Answer 4

Heavy interstitial infiltration with eosinophil and granulomas

Question 5

What are some key signs of acute glomerulonephritis?

Answer 5

• Oligo/anuria
• Haematuria
• Erythrocyte and leukocyte casts on MCS

Question 6

What is rapidly progressive (crescentic) GN?

Answer 6

Most aggressive form of GN – can cause ESRF within weeks.

Presents as a nephritic syndrome, but oliguria and renal failure are more pronounced

Question 7

What causes crescents to appear in acute glomerulonephritis?

Answer 7

Occurs in severe glomerulonephritis due to proliferation of macrophages & parietal cells in Bowman’s space which pushes glomerulus to one side

Question 8

Describe the classification of acute crescentic glomerulonephritis.

Answer 8

Classification based on immunological findings:

• Type 1. Anti-GBM antibody (Goodpasture’s)
• Type 2. Immune complex mediated (SLE)
• Type 3. Pauci-immune (ANCA-associated - GPA)

NOTE: these can rapidly lead to irreversible renal failure

Question 9

List some causes of immune complex-associated (type 2) crescentic glomerulonephritis.

Answer 9

• SLE
• IgA nephropathy
• Post-infectious glomerulonephritis
• HSP

Question 10

What techniques can be used to visualise immune complexes in these diseases?

Answer 10

• Immunohistochemistry (fluorescence microscopy)
• Electron (light) microscopy

Question 11

How does immune complex-associated crescentic GN appear on fluorescence microscopy?

Answer 11

Granular (lumpy bumpy) IgG immune complex deposition on GBM/mesangium

Question 12

What are the antibodies directed against in anti-GBM disease?
How can these antibodies be detected?

Answer 12

• Against the C-terminal domain of type IV collagen (COL4-A3)
• Detected by serology

NOTE: these antibodies can cross-react with the alveolar basement membrane leading to pulmonary haemorrhage and haemoptysis

Question 13

Describe the immunohistochemistry picture produced in anti-GBM disease

Answer 13

Linear deposition of IgG on the glomerular basement membrane

Question 14

What are the main features of pauci-immune crescentic glomerulonephritis?

Answer 14

• Lack of / scanty glomerular immunoglobulin depositis
• Usually associated with ANCA
• Triggers neutrophil activation and glomerular necrosis
• Vasculitis (elsewhere) – particularly presenting as skin rashes or pulmonary haemorrhage

Question 15

What is thrombotic microangiopathy?

Answer 15

• Damage to the endothelium in glomeruli, arteriols and arteries resulting in thrombosis
• Red cells can be damaged by fibrin causing MAHA or HUS

Question 16

List some types of thrombotic microangiopathy.

Answer 16

HUS: Thrombi confined to kidneys

• Typical HUS - usually associated with diarrhoea caused by E.coli O157:H7 (outbreaks caused by children visiting petting zoos/eating undercooked meat)
• Atypical HUS (non-diarrhoea associated) - due to abnormal proteins in complement pathway/endothelium (can be familial)
• Triad - thrombocytopaenia, MAHA, renal damage

TTP: Thrombi occur throughout circulation, esp. in CNS

• A genetic / acquired deficiency of ADAMTS13
• Pentad - thrombocytopaenia, MAHA, renal damage, CNS abnormalities, fever

Also:

• Drugs, radiation, hypertension, scleroderma, antiphospholipid syndrome

Question 17

What are the characteristic features of nephrotic syndrome?

Answer 17

• Proteinuria (>3.5 g/day or >300mg/mmol PCR)
• Hypoalbuminaemia
• Oedema
• Hyperlipidaemia

Question 18

List some causes of nephrotic syndrome.

Answer 18

• Primary glomerular disease (non-immune complex mediated)
  
  • Minimal change disease
  • Focal segmental glomerulosclerosis
• Primary renal disease (immune complex mediated)
  
  • Membranous glomerulonephritis
• Systemic disease
  
  • SLE
  • Amyloidosis
  • Diabetes mellitus

Question 19

What is minimal change disease?

Answer 19

• Most common cause of nephrotic syndrome in children
• Glomeruli look normal on light microscopy, but electron microscopy shows loss of foot processes
• Generally responds well to steroids and immunosuppression

Question 20

Describe the histological appearance of focal segmental glomerulosclerosis.

Answer 20

Focal and segmental glomerular consolidation and scarring
Hyalinosis

NOTE: this responds less well to immunosuppression